ESI‐MS investigation of solvent effects on the chiral recognition capacity of tartar emetic towards neutral side‐chain amino acids

Abstract

The effect of solvent systems on previously-reported ESI-MS based proton-assisted enantioselective molecular recognition phenomena of tartar emetic, L-antimony(III)-tartrate, was evaluated. This was achieved by carrying out a series of competitive binding experiments using chiral selectors, bis(sodium) D- and -L-antimony(III)-tartrates with chiral selectands, neutral side-chain amino acid enantiomeric isotopomers of alanine (Ala), valine (Val), leucine (Leu) and phenylalanine (Phe), in three different solvent systems, ACN/H(2)O (75/25 v/v), H(2)O (100%) and H(2)O/MeOH (25/75 v/v). Observations from these experiments suggest that the effect of solvent systems on previously reported proton-assisted chiral recognition capacity of D,L-antimony(III)-tartrates is small, but not negligible. It was observed that an ACN/H(2)O (75/25 v/v) solvent system facilitates and enhances the chiral discrimination capacity of protonated {[D,L-Sb(2)-tar(2)][H]}(-) ionic species. Further, amino acid enantiomers showed a general trend of increasing selectivity order, Val ≤ Ala < Leu ≈ Phe towards the protonated {[D,L-Sb(2)-tar(2)][H]}(-) ionic species which was independent of the solvent system employed. The lack of enantioselective binding for {[D,L-Sb(2)-tar(2)]}(2-) ionic species was consistently recorded in respective mass spectra from all performed experiments, which suggests that ESI-friendly solvent systems have no effect and do not influence this phenomenon.

Solvent Molecules Undergo Homolytic Cleavage and Radical Recombination Processes during Negative-Mode Electrospray Ionization: Adduct Formation with Antimony(III)-Tartrate Dianion

“…In order to obtain more insight into their enantioselective character, we investigated the solution and gas-phase binding of antimony(III)-D,L-tartrates to several neutral amino-acids using ESI-MS and MS/MS. 12,18,19 While these were not the first studies of antimony(III)-tartrate recognition by ESI-MS, 20,21 they did reveal, for the first time, the presence of an enantioselective recognition phenomenon, whereby different charge states of the chiral selector showed different binding selectivities toward neutral amino acid enantiomers.…”

“…While further investigation of enantioselective recognition phenomena for antimony(III)-tartrate continues, this manuscript reports a rather serendipitous finding, which arose from those previous studies. 12,18,19 Detailed investigation of negative-ionization mode ESI-mass spectra have allowed us to show that the dianionic antimony(III)-tartrate ([Sb 2 -tar 2 ] 2-) complex is capable of adducting to neutral solvent reaction products that are generated during the negative-ionization mode electrospray process. New experimental insight regarding the participation of solvent molecules during negative-ionization mode ESI was revealed by carrying out a systematic variation of solvent composition and ionization parameters.…”

New structural insight for antimony(III)-tartrate

“…Enantioselective molecular recognition properties of tartar emetic in solution and in the gas phase have often been explained based on this particular geometry [5]. However, explicating our observations [7][8][9][10], particularly the proton-assisted enantioselective character of tartar emetic was not trivial using this particular structure alone. Also, in several instances, it was mentioned that the anti-parasitic and anti-bacterial activity of tartar emetic is still not fully understood [2,3].…”

“…Since Na 2 [Sb 2 -L-tar 2 ] and K 2 [Sb 2 -L-tar 2 ] are only sparingly soluble in dimethylsulfoxide (DMSO), [P(Bu) 4 ] 2 [Sb 2 -L-tar 2 ] was prepared (Scheme 1, using methods described in literature [1]) and used instead. DMSO was selected as the solvent for these analyses to eliminate proton abstraction by the antimony(III)-tartrate dianion [7][8][9][10]. During the Observation of the peaks labeled with 2p and 2q (observed at δ (ppm) = 4.5 and 3.3, respectively) along with the peak labeled with 1 (observed at δ (ppm) = 4.2) clearly illustrate the co-existence of the isomeric structures predicted for the gas phase.…”

“…Our recent attempts to understand its chiral biomolecular recognition capacity using electrospray ionization-mass spectrometry (ESI-MS) uncovered an unprecedented proton-assisted enantioselective character of tartar emetic for binding of neutral side-chained amino acids (Ala, Val, Leu and Phe) [7][8][9]. More specifically, it was observed that, in order for tartar emetic to show enantioselective association/dissociation phenomena, a proton association to the antimony(III)-L-tartrate dianionic core was crucial.…”